Update: role of the angiotensin type-2 (AT(2)) receptor in blood pressure regulation.

In the past, virtually all of the physiologic actions of angiotensin II (ANG II) were thought to be mediated by the type-1 ANG II receptor. However, there is now a compelling body of evidence suggesting that the type-2 (AT2) receptor is an important regulator of renal function and blood pressure (BP). The AT2 receptor stimulates a bradykinin (BK)-nitric oxide (NO)-cyclic GMP vasodilator cascade in blood vessels and in the kidney. Recent studies have shown that absence of the AT2 receptor lends to pressor and natriuretic hypersensitivity to ANG II. Furthermore, there is now excellent evidence that the AT2 receptor mediates pressure natriuresis. The AT2 receptor also stimulates the conversion of prostaglandin E2 (PGE2) to PGF2. In addition, it is now apparent that the therapeutic reduction in BP with AT1 receptor blockade (eg, losartan, valsartan, candesartan) is mediated by ANG II stimulation of the AT2 receptor, leading to increased levels of BK, NO, and cGMP. Current evidence predicts that AT2 receptor agonists would be beneficial in the treatment of hypertension.